Neurodegeneration and Dementia Flashcards
1
Q
name examples of diagnostic tools for dementia
A
- neuroimaging (PET, MRI-volumetry)
- CSF biomarkers
- psychometric tests
2
Q
outline the processes of the amyloid cascade (according to the amyloid hypothesis/theory)
A
APP cut by secretases → Ab-peptide → amyloid species → soluble oligomers (which are now considered to be synaptotoxic) → amyloid fibrillies → b-amyloid plaques → neuroinflammation → tau tangles
3
Q
what are the two opposing theories on amyloid and tau pathology?
A
- amyloid theory - tau is merely a result of the amyloid cascade, but is not a main cause of the disease
- tau-protein theory - disturbed axonal transport and protein metabolism leads to amyloid plaques, which are not themselves essential to the disease
4
Q
He et al., 2017 study on tau vs. amyloid development
A
- mice injected with tau vs. amyloid
- injecting amyloid led to tau tangles, but injecting tau did not lead to amyloid plaques
- Ab-protein levels drop → amyloid plaques increase → tau tangles
5
Q
describe subjective cognitive decline (SCD)
A
- stage prior to MCI
- identified with biomarkers, and patients start recognizing mild symptoms
- the symptoms cannot yet be determined using psychometric tests
6
Q
Alzheimer’s Disease genetics
A
- APOE e4e4 increases the association between amyloid depositions and subsequent development of AD (homogenous APOE-4 carriers) - 90% risk of developing AD by the age of 90
- APOE e2e4 increases the association between amyloid depositions and subsequent development of AD (heterogeneous APOE-4 carriers), but not as significantly as APOE e4e4
- Familiar cases - mutations in three different genes, which subsequently increase the risk of developing AD
7
Q
what are Amyloid-Related Imaging Abnormalities (ARIAs) and what kinds exist?
A
- Imaging findings detected on MRI, which are associated with the investigational use of monoclonal antibodies targeting amyloid-β, including aducanumab
- ARIA-H - hemosiderin deposits (small hemorrhages)
- ARIA-E - cerebral edema (fluid accumulation)
8
Q
main risk factors
A
- non-degenerative dementias - high blood pressure, diabetes, depression, other lifestyle factors
- degenerative dementias - old age is the main risk factor for neurodegenerative diseases causing dementia (+ genetics)
9
Q
clinical trial outcomes
A
- monoclonal antibody treatments
- Aducanumab
- Lecanemab - recently approved by FDA
- not ideal for all patients, but effective for many (slows down disease progression - amyloid accumulation as well as symptom development for several months, up to 1.5y so far)